I. Field of the Invention
This invention relates to freeze-dried pharmaceutical preparations containing antibacterial quinolinecarboxylic acid derivatives which preparations exhibit excellent stability against light and heat and rapid splubility.
II. Description of the Prior Art
In this invention, the antibacterial quinoline-carboxylic acid derivatives have the following general formula (I), ##STR1## wherein R.sup.1 represents a cycloalkyl group having 3 to 6 carbon atoms, straight or branched lower alkyl group, lower haloalkyl group, lower alkenyl group, lower hydroxyalkyl group, lower alkylamino group or substituted or unsubstituted phenyl groupl; R.sup.2 represents a hydrogen atom, halogen atom, nitro group or amino group; X.sup.1 represents a halogen atom; Y represents a nitrogen atom or CX.sup.2, (wherein X.sup.2 represents a hydrogen atom, halogen atom, lower alkyl or alkoxy group, or X.sup.2 and R.sup.1 together are atom, lower alkyl alkoxy group, or X.sup.2 and R.sup.1 together are --O--CH.sub.2 CH(CH.sub.3)--, --CH.sub.2 CH.sub.2 CH(CH.sub.3)--, --CH.sub.2 CH(CH.sub.3)--), Z represents ##STR2## wherein n is 1 or 2. R.sup.3 represents a hydrogen atom or lower alkyl group, R.sup.4 and R.sup.5 each represent independently a hydrogen atom, lower alkyl group, lower aminoalkyl group, lower hydroxyalkyl group or phenyl group or ##STR3## wherein k is 0 or 1, l is 0, 1 or 2, R.sup.6 represents a hydrogen atom, halogen atom, lower alkyl group or hydroxy group, R.sup.7 represents a hydrogen atom, lower alkyl group, lower haloalkyl group or lower hydroxyalkyl group, R.sup.8 represents a hydrogen atom or lower alkyl group; the hydrates or the pharmaceutically acceptable acid addition or alkali salts thereof. (As used herein, "lower" when used in connection with alkyl or alkenyl means having 1 to 3 carbon atoms.)
It is known that most of these compounds have relatively low solubility in water. There have been a variety of studies to improve the solubility. For instance, a solution of antibacterial quinolinecarboxylic derivatives could be prepared by adding lactic acid or the like (Japanese Laid-Open Patent Application Sho 60-94910 which corresponds to EP-A-0 138 018) or alkali (Japanese Laid-Open Patent Application Sho 61-180771 which corresponds to EP-A-0 187 315).
However, even after the dissolution of the compounds in water was achieved, it was difficult to develop a stable pharmaceutical solution satisfactory for parenteral use, because the solution easily discolored under exposure to light or by heating and formed some decomposed materials. Therefore, a pharmaceutical solution containing antibacterial quinolinecarboxylic acid derivative suitable for parenteral use has not been achieved by these procedures.